Last month, a critical paper was published in Genes and Development by researchers at MIT, The Broad Institute and Dana Farber, highlighting the discovery of Nuclear Factor I/B (NFIB), which may play a key role in small cell lung cancer (SCLC). I thought I had reviewed the NFIB oncogene already, but it never made it out of Drafts. Time to fix that omission!
Regular readers will remember the recent discussions of other findings by some of the same researchers (Nathanael Gray and Matthew Myerson) in squamous cell carcinoma, a subset of non-small cell lung cancer (NSCLC), such as the DDR2 and FGFR1 mutations. The group, along with Levi Garraway and Tyler Jacks, are very active in lung cancer research.
Small cell carcinoma is a different disease though, affecting approximately 15% of all lung cancer cases. Sadly though, 95% of people who are diagnosed with the disease are no longer with us at five years, so the overall survival rate is fairly poor. This happens partly because it is a very aggressive disease, and partly because it tends to be diagnosed late.
We don’t know what the driver genes in SCLC are, so chemotherapy has been very much the bedrock of treatment for many years and as far as I know, there are no approved targeted agents for SCLC.
In the current research, Dooley et al., (2011) described how they used whole gene profiling to find a new oncogene that was present in both the mouse model (with two key tumor-suppressor genes, p53 and Rb, deleted) and in patients with SCLC:
“Using a genetically engineered mouse model of SCLC driven by conditional deletion of Trp53 and Rb1 in the lung, we identified several frequent, high-magnitude focal DNA copy number alterations in SCLC.
We uncovered amplification of a novel, oncogenic transcription factor, Nuclear factor I/B (Nfib), in the mouse SCLC model and in human SCLC.”
This is the first time NFIB has been reported in SCLC, but it has been observed in mouse studies in prostate cancer. It is a significant finding, because as the authors note:
“This model provided a platform with which to identify genetic alterations that occur during tumor progression.”
The NFIB gene codes for a transcription factor, which means it controls the expression of other genes, so researchers in Jacks’ lab are now looking for the genes controlled by NFIB. As Dooley observed:
“If we find what genes NFIB is regulating, that could provide new targets for small cell lung cancer therapy.”
Overall, this is thorough and very promising research in SCLC that matches activity in animals with patients. I’m looking forward to the next installment when we will hopefully learn what the potential targets are. Once we have that information, there will either be currently approved agents that can be tested, others in clinical development, or even new compounds that will need to be designed for the purpose.
The good news is that progress is being made – that’s always heartening to hear.
Dooley, A., Winslow, M., Chiang, D., Banerji, S., Stransky, N., Dayton, T., Snyder, E., Senna, S., Whittaker, C., Bronson, R., Crowley, D., Barretina, J., Garraway, L., Meyerson, M., & Jacks, T. (2011). Nuclear factor I/B is an oncogene in small cell lung cancer Genes & Development, 25 (14), 1470-1475 DOI: 10.1101/gad.2046711